The overall goal of the proposed study is to identify neurophysiological and behavioral markers of sensitivity to smoking cessation treatment. Although smoking widely recognized as the major preventable cause of death and substantial proportion of smokers try to quit every year, quit attempts often fail within the first week due to smokers'inability to abstain from smoking in the face of rapidly developing withdrawal symptoms. We hypothesize that success of smoking cessation treatment critically depends on individual differences in the cognitive control processes that play a key role in inhibitory regulation of behavior including response inhibition, action monitoring, and reward/punishment sensitivity. We further hypothesize that these processes are compromised by acute nicotine deprivation, which facilitates relapse to smoking. However, little is known about the effects of deprivation on cognitive control processes in the context of smoking cessation treatment and the lack of objective physiological and behavioral markers that could predict the sensitivity to smoking cessation intervention is a major challenge in the translational research on nicotine addiction. In the proposed study, we will examine the utility of event-related potentials (ERPs) and behavioral measures of cognitive control as phenotypic markers of sensitivity to smoking cessation intervention. Participants will be 150 smokers all of whom will be motivated to receive cognitive-behavioral smoking cessation treatment. Specific Aims are 1) to examine the effects of baseline individual differences in neurophysiological and behavioral indices of cognitive control and reward sensitivity on the outcome of smoking cessation intervention, 2) to examine acute effects of nicotine deprivation on neurocognitive indicators of self-regulation and to determine whether individual differences in susceptibility to these effects predict the outcome of smoking cessation treatment, and 3) to examine the effects of biologically relevant genetic variation in the brain dopamine system on deprivation-induced changes in brain function and the outcome of smoking cessation treatment. Potential impact of the study is two-fold: first, it will provide intermediate phenotypes that predict sensitivity to behavioral interventions;second, it will elucidate neurocognitive mechanisms mediating the relationship between nicotine deprivation and smoking relapse. This knowledge can be used for the development of more efficient smoking cessation treatment approaches and for better tailoring of specific treatments to individuals who are most likely to benefit. The proposed study is aimed at the identification of neurobehavioral predictors of the outcome of a smoking cessation intervention. The study will examine brain function underlying self-control of behavior in smokers participating in a smoking cessation treatment, both before quitting and after quitting, in order to determine how individual differences in brain responses to nicotine abstinence are associated with changes in behavior such as increased impulsivity, and how they predict the outcome of treatment (successful quitting versus relapse). This knowledge can be used for the development of more efficient smoking cessation treatment approaches and for better tailoring of specific treatments to individuals who are most likely to benefit. Ultimately, the knowledge of "neurobehavioral profiles" associated with sensitivity to treatment can lead to the development of individualized treatment plans, e.g. those emphasizing behavioral or pharmacological intervention, or some combination of these approaches. Furthermore, identification of specific neural processes that critically affect the outcome of smoking cessation can suggest new targets for pharmacological intervention.